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Current advances in medicine have revolutionized the field of regenerative medicine dramatically with newly evolved therapies for repair or replacement of degenerating or injured tissues. Stem cells (SCs) can be harvested from different sources for clinical therapeutics, which include fetal tissues, umbilical cord blood, embryos, and adult tissues. SCs can be isolated and differentiated into desired lineages for tissue regeneration and cell replacement therapy. However, several loopholes need to be addressed properly before this can be extended for large-scale therapeutic application. These include a careful approach for patient safety during SC treatments and tolerance of recipients. SC treatments are associated with a number of risk factors and require successful integration and survival of transplanted cells in the desired microenvironment with concurrent tissue regeneration. Recent studies have focused on developing alternatives that can replace the cell-based therapy using paracrine factors. The development of stem "cell free" therapies can be devoted mainly to the use of soluble factors (secretome), extracellular vesicles, and mitochondrial transfer. The present review emphasizes on the paradigms related to the use of SC-based therapeutics and the potential applications of a cell-free approach as an alternative to cell-based therapy in the area of regenerative medicine., (© 2017 International Union of Biochemistry and Molecular Biology, Inc.)

[Display omitted] • Hallmarks of Alzheimer's disease like pathology were recapitulated in differentiated mature SH-SY-5Y cells with Aβ oligomer and streptozotocin in separate in vitro models. • Autonomous mitochondria isolated from dental pulp stem cells (DPSC) were internalized by co-culture with mature neurons and showed no cellular toxicity. • Mitochondria internalization in AD-induced SH-SY-5Y cells showed amelioration of neuronal loss and ROS production. Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognition decline and memory deterioration. The molecular pathogenic mechanism of AD is highly complex and still not completely clarified. While stem cell-based therapy for AD has been considered an optimal choice with specific properties however, immune rejection and risk of malignant transformation limit their therapeutic application. Growing evidence suggest that mitochondrial dysfunction has a critical role in the progression of AD. Since there have not been any effective treatment for AD, the drugs targeted to mitochondria may hold a great promise Therefore, the major objective of this study is to evaluate the therapeutic applicability of transplanting MSCderived mitochondria as a neuroprotective biomolecule in Alzheimer's disease pathology. The hallmarks of AD i.e aggregation of Aβ protein and Tau protein were generated to mimic the AD like pathology in vitro. Further, morphology analysis, cell viability assay, and immunofluorescence assay have been done for validation. Mitochondria were isolated from dental pulp stem cell (DPSC) and their effect on internalization by neural cells was demonstrated by cell proliferation analysis and uptake studies while their therapeutic potential was characterized by morphology analysis, ROS study, and immunofluorescence analysis. We observed that internalization of DPSC-derived mitochondria led to significant neuroprotective in the cellular AD. Based on our results, it may be concluded that mesenchymal stem cellderived mitochondria can emerge as a potentially safe and effective modality in Alzheimer's disease. [ABSTRACT FROM AUTHOR]